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      HIV Phylogeographic Analyses and Their Application in Prevention and Early Detection Programmes: The Case of the Tijuana–San Diego Border Region

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          Abstract

          As the deadline for the UNAIDS 90–90–90 target approaches, huge challenges in HIV diagnosis, access to treatment and follow up have become evident. This initiative aims to have 90% of people living with HIV diagnosed, 90% of diagnosed people receiving antiretroviral therapy (ART) and 90% of people receiving ART under viral suppression by 2020 (http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf, n.d.). In this regard, huge improvements have been made on ART programmes around the world, especially in resource-limited settings. Nevertheless, identifying new and undiagnosed HIV infections is an important issue in large areas of the world where stigmatization and ignorance towards HIV infection and its transmission routes still prevail. This is the case of most Latin American countries, which generally present concentrated epidemics with a wide variety of epidemiological scenarios, most of which are characterized by late presentation of individuals living with HIV to clinical care (Crabtree-Ramirez et al., 2011). In Mexico, a middle-income country with a strong ART programme, it is estimated that more than half of HIV-infected individuals are unaware of their serologic status (http://www.censida.salud.gob.mx/descargas/2009/VIHSIDAenMexico2009.pdf, n.d.). Cases like this render ART programmes alone unable to control the epidemics and constitute a major challenge for the ambitious 90–90–90 target to become a reality. Knowledge on HIV transmission dynamics is needed in order to focus and strengthen prevention and early detection programmes, urgently needed in Latin America. In recent years, HIV phylogenetic and phylogeographic analyses have been ever more recognized as a fundamental tool for studying HIV transmission dynamics, which can result in the generation of public health policies improving HIV prevention programmes (Grabowski & Redd, Mar 2014). Phylogenetic and clustering analyses can provide useful information on clinical and demographic factors shaping HIV transmission in specific geographic areas, and when geographic data is available, can identify the specific location and spread of HIV transmission hotspots. Large multinational efforts such as PANGEA-HIV (Pillay et al., Mar 2015) have been created to use viral sequence data to assess transmission of HIV in the context of generalized epidemics. Moreover, recent studies have demonstrated the possibility of identifying HIV transmission hotspots in near real time by the secondary phylogenetic analysis of HIV sequences obtained for routine drug resistance testing in concentrated epidemics with a high sampling density (Poon et al., 2015). In this issue of E-Biomedicine, Mehta et al. (Mehta et al., 2015) present a phylogeographic study to assess the characteristics of HIV transmission in the Tijuana–San Diego crossing of the Mexico–U.S. border region. This work is a good example of how phylogenetic and phylogeographic analyses on already existing HIV sequence data can provide useful information on HIV transmission dynamics in an especially complex HIV transmission hotspot. The Tijuana–San Diego border is probably the busiest land border crossing in the world, characterized by a large transnational commercial sex network, a large population of people who inject drugs (PWID), and a large population of men who have sex with men (MSM) (Strathdee et al., 2012). The prostitution district in Tijuana is frequented by thousands of U.S. and foreign tourists each year and this region geographically overlaps with a neighbourhood known for its high density of PWID. Risk behaviour for HIV acquisition is high in the border region and is strongly associated with economic disparities, with a high frequency of male clients negotiating condom-less sex with female sex workers (FSW), who accept higher rates for unprotected sex out of economic necessity and are also often PWID (Strathdee et al., 2012, Martinez-Donate et al., 2015, Robertson et al., 2014). In their study, Mehta et al. describe the epidemics in Tijuana and San Diego as highly separated, the last one dominated by MSM clusters. Nevertheless, the authors identified bidirectional mixed international clusters including FSW, PWID and MSM, describing this border region as a “melting pot” of risk groups. International clusters had higher proportion of females, heterosexuals and PWID, highlighting the importance of commercial sex in HIV transmission across the border and pointing areas of opportunity for prevention interventions. Moreover, albeit with considerable overlap in both directions, a shift in viral migration from Tijuana to San Diego was observed comparing 2014 to the 1990s, when the opposite was true. It is important to mention that even with a relatively low sampling density, clusters providing useful epidemiological information were found yielding useful conclusions to inform public health policies. Also, the lack of male individuals in clusters including FSW is also informative as it underscores the need to focus detection efforts in their customers and partners. Following WHO recommendations to implement HIV drug resistance (DR) surveillance in the region, many Latin American countries are making efforts to implement HIVDR surveys nationally, with the support of WHO-accredited national and regional laboratories. Thus, even with an important limitation in sequencing capacity, generation of HIV sequence data linked to basic socio-demo-geographic data is expected to grow significantly in the next few years. These data could also be used in phylogenetic and transmission network analysis to inform HIV transmission dynamics in the region, always with a cautious interpretation due to sampling limitations. Eventually, these data could improve targeting of prevention and early detection efforts to place this region of the world closer to the 90–90–90 target in 2020. Disclosure The authors declare no conflicts of interest.

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          The emerging HIV epidemic on the Mexico-U.S. border: an international case study characterizing the role of epidemiology in surveillance and response.

          Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome surveillance data are critical for monitoring epidemic trends, but they can mask dynamic subepidemics, especially in vulnerable populations that underuse HIV testing. In this case study, we describe community-based epidemiologic data among injection drug users (IDUs) and female sex workers (FSWs) in two northern Mexico-U.S. border states that identified an emerging HIV epidemic and generated a policy response. We draw from quantitative and qualitative cross-sectional and prospective epidemiologic studies and behavioral intervention studies among IDUs and FSWs in Tijuana, Baja California, and Ciudad Juarez, Chihuahua. The recognition that the HIV epidemic on Mexico's northern border was already well established in subgroups in whom it had been presumed to be insignificant was met with calls for action and enhanced prevention efforts from researchers, nongovernmental organizations, and policy makers. Successful policies and program outcomes included expansion of needle-exchange programs, a nationwide mobile HIV prevention program targeting marginalized populations, a successful funding bid from the Global Fund for HIV, TB, and Malaria to scale up targeted HIV-prevention programs, and the establishment of bi-national training programs on prevention of HIV and substance use. We discuss how epidemiologic data informed HIV prevention policies and suggest how other countries may learn from Mexico's experience. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Molecular tools for studying HIV transmission in sexual networks.

            Phylogenetics is frequently used for studies of population-based HIV transmission. The purpose of this review is to highlight the current utilities and limitations of phylogenetics in HIV epidemiological research from sample collection through to data analysis.
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              HIV Transmission Networks in the San Diego–Tijuana Border Region

              Background HIV sequence data can be used to reconstruct local transmission networks. Along international borders, like the San Diego–Tijuana region, understanding the dynamics of HIV transmission across reported risks, racial/ethnic groups, and geography can help direct effective prevention efforts on both sides of the border. Methods We gathered sociodemographic, geographic, clinical, and viral sequence data from HIV infected individuals participating in ten studies in the San Diego–Tijuana border region. Phylogenetic and network analysis was performed to infer putative relationships between HIV sequences. Correlates of identified clusters were evaluated and spatiotemporal relationships were explored using Bayesian phylogeographic analysis. Findings After quality filtering, 843 HIV sequences with associated demographic data and 263 background sequences from the region were analyzed, and 138 clusters were inferred (2–23 individuals). Overall, the rate of clustering did not differ by ethnicity, residence, or sex, but bisexuals were less likely to cluster than heterosexuals or men who have sex with men (p = 0.043), and individuals identifying as white (p ≤ 0.01) were more likely to cluster than other races. Clustering individuals were also 3.5 years younger than non-clustering individuals (p < 0.001). Although the sampled San Diego and Tijuana epidemics were phylogenetically compartmentalized, five clusters contained individuals residing on both sides of the border. Interpretation This study sampled ~ 7% of HIV infected individuals in the border region, and although the sampled networks on each side of the border were largely separate, there was evidence of persistent bidirectional cross-border transmissions that linked risk groups, thus highlighting the importance of the border region as a “melting pot” of risk groups. Funding NIH, VA, and Pendleton Foundation.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                01 September 2015
                October 2015
                01 September 2015
                : 2
                : 10
                : 1296-1297
                Affiliations
                Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico
                Author notes
                Article
                S2352-3964(15)00152-8
                10.1016/j.ebiom.2015.08.039
                4634359
                d2b3f5f9-4370-4e42-bffb-373e17344db0
                © 2015 The Authors. Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                hiv transmission dynamics,phylogeographic analysis,tijuana–san diego,mexico,u.s.,latin america

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